Methods for responsively treating neurological disorders

ABSTRACT

Disclosed is a multiple electrode, closed-loop, responsive system for the treatment of certain neurological diseases such as epilepsy, migraine headaches and Parkinson&#39;s disease. Brain electrodes would be placed in close proximity to the brain or deep within brain tissue. When a neurological event such as the onset of an epileptic seizure occurs, EEG signals from the electrodes are processed by signal conditioning means in a control module that can be placed beneath the patient&#39;s scalp, within the patient&#39;s chest, or situated externally on the patient. Neurological event detection means in the control module will then cause a response to be generated for stopping the neurological event. The response could be an electrical signal to brain electrodes or to electrodes located remotely in the patient&#39;s body. The response could also be the release of medication or the application of a sensory input such as sound, light or mechanical vibration or electrical stimulation of the skin. The response to the neurological event can originate from devices either internal or external to the patient. The system also has the capability for multi-channel recording of EEG related signals that occur both before and after the detection of a neurological event. Programmability of many different operating parameters of the system by means of external equipment provides adaptability for treating patients who manifest different symptoms and who respond differently to the response generated by the system.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present invention is a continuation of co-pending U.S. patentapplication Ser. No. 09/628,977, filed Aug. 2, 2000, which is acontinuation of U.S. patent application Ser. No. 09/450,303, filed Nov.29, 1999, now U.S. Pat. No. 6,128,538, which is in turn a continuationof U.S. patent application Ser. No. 08/957,869, filed Oct. 27, 1997, nowU.S. Pat. No. 6,016,449.

FIELD OF THE INVENTION

[0002] This invention is in the field of devices for the treatment ofneurological disorders in human subjects, particularly those disordersthat originate in the brain.

BACKGROUND OF THE INVENTION

[0003] The current state of the art in treating neurological disorderssuch as epilepsy or Parkinson's disease involves either drugs or theopen-loop electrical stimulation of neurologic tissue. Drug therapy hasbeen shown to have significant short and long term side effects and isoften ineffective. In U.S. Pat. No. 3,850,161, Liss describes acontinuous closed-loop feedback system which will always feedback partof the brain EEG signal to separate electrodes so that if a large EEGsignal occurs it will be fed back in an attempt to cancel out theoriginal signal. This system does not take advantage of recentlydeveloped digital signal processing and microcomputer technology bywhich feedback signals can be activated only when a neurological eventoccurs, nor does it provide a practical means to recognize and interveneduring early stages in the evolution of a neurological event. Inaddition, the Liss device is not programmable and it does not provide ameans to record EEG signals. Examples of a “neurological event” are theoccurrence of an epileptic seizure or the occurrence of a migraineheadache. A “neurological event” is defined herein as either theprecursor of an event such as an epileptic seizure, or the epilepticseizure itself.

[0004] Maurer and Sorenson in U.S. Pat. No. 4,019,518 describe acombined internal/external system for electrical stimulation of the bodywith biphasic pulses but do not describe any means of detectingneurological events. Fischell in U.S. Pat. No. 4,373,527 describes aprogrammable medication infusion system but does not anticipate its usein response to a detected neurological event.

[0005] More recently, a device has been approved for human use tostimulate the vagus nerve in a continuous fashion with the objective ofdecreasing the rate of epileptic seizures. Clinical reports on suchdevices indicate only a modest degree of success in that only 50% of thepatients experience a greater than 20% reduction in the rate ofepileptic seizures. Another device that has been recently introducedinto clinical practice utilizes continuous stimulation of the thalamusfor the treatment of involuntary motion disorders such as Parkinson'ssyndrome.

[0006] Neither of these two open-loop devices described above is highlyeffective for the treatment of a neurological disorder such as epilepsy,and neither anticipates the use of decision making in order to optimizea response to turn off the neurological event nor the recording of EEGsignals.

[0007] The automatic implantable cardiac defibrillator is an example ofa decision making device having data recording capability that has beensuccessfully used in a decision based closed-loop mode for the treatmentof ventricular fibrillation. However, the requirements for detection andtreatment of ventricular fibrillation are significantly simpler andcertainly different from the requirements for a device to detect andtreat an impending epileptic seizure. Specifically, an implantablecardiac defibrillator requires only a single signal, namely the heart'sECG, in order to detect a fibrillation event. What is more, only asingle pair of electrodes is required for detection of the fibrillationevent and that same pair of electrodes can be used to provide anelectrical stimulus for electrical defibrillation. A heart defibrillatorelectrode is adapted to be placed on or in close proximity to the heartand is not suitable for use as a brain electrode.

[0008] Coker and Fischell in U.S. Pat. No. 4,581,758 describesophisticated signal processing techniques using the sum of squaredsignals from two microphones to identify the direction with respect to aperson from whom human speech originates. Although the Coker andFischell patent teaches several signal processing techniques which maybe applied with others to detect neurological events, the Coker andFischell method is aimed at identifying the location of the speechsource, while one of the goals of the present invention is to utilizethe known location of the source of EEG signals to help identify anabnormal EEG which signifies an impending neurological event.

[0009] The NeuroCybernetic Prosthesis System recently made available forthe treatment of epileptic seizures, utilizes continuous open-loopstimulation of the vegas nerve. This device does not sense the onset ofan epileptic seizure, and it utilizes wires that are placed in the neck.Because of the frequent motions of such wires, they will have a tendencyto fracture. No existing system utilizes electrodes, electrical wiresand a control module that are entirely contained within the patient'sscalp and essentially all contained within the patient's cranium. Suchsystems would not have any repeated bending of connecting wires therebyimproving long term reliability. Furthermore, the NeuroCyberneticProsthesis System does not use a rechargeable battery, nor does itutilize a separate external device controlled by the patient to activatethe implanted system at the start of a neurological event in order todecrease the severity or time duration of the neurological event.

SUMMARY OF THE INVENTION

[0010] The present invention is a multiple electrode, closed-loop systemfor the treatment of certain neurological disorders such as epilepsy,migraine headaches and Parkinson's disease. A purpose of the presentinvention is to overcome the shortcomings of all prior art devices forthe treatment of such disorders. Specifically, the present inventioncombines a multi-electrode array with sophisticated signal processingtechniques to achieve reliable detection of the onset of a neurologicalevent (such as an epileptic seizure or migraine headache) typicallyoriginating from a focus of limited spatial extent within the brain. Itis well known that in certain patients, epileptic seizures consistentlyoriginate from a single location within the brain. However, the systemdescribed herein is also adaptable for the treatment of a neurologicalevent that involves a major portion or possibly all of the brain tissue.

[0011] The present invention also provides means for generating anensemble of coordinated electrical stimuli designed to terminate theneurological event immediately upon (or even prior to) its onset. Thus,the present invention is a responsive detection and stimulation systemfor the early recognition and prompt treatment of a neurological event.

[0012] The present invention envisions a multiplicity of brainelectrodes placed either within the brain, on the surface of the brainitself, or on the dura mater that surrounds the brain. Some one,several, or all of these brain electrodes can be used for detection ofan abnormal neurological event such as an epileptic seizure. Aresponsive stimulation signal can also be applied to any one, several,or all elements of such an electrode array. The responsive stimulationsignals sent to each electrode may be identical or they may beprogrammed to differ in amplitude, frequency, waveform, phase and timeduration. It is also envisioned that sensing electrodes may be entirelyseparate from the electrodes used for responsive stimulation.

[0013] The present invention envisions that a neurological event can bereliably detected in the presence of a normal EEG signal and in thepresence of external noise by the use of modern and sophisticated signalprocessing techniques. Specifically, the electrical signal from anepileptic focus within a specific and limited spatial region within thebrain can be reliably detected by combining the signals received atdifferent electrodes that are placed at different distances from theepileptic focus. To improve signal-to-noise ratio, the signal receivedat a specified location which is at a specific distance from theepileptic focus could have a specific time delay to account for thepropagation time it takes for the signal to reach that electrode. Forexample, if a first electrode is located directly over the site of theepileptic focus and a second electrode is located at a distance ofseveral centimeters from the focus, then to combine these two signalstogether to optimize detection of a neurological event, the signal atthe first (closest) electrode must have an added time delay to accountfor the time required for the signal to arrive at the position of thesecond electrode. Thus cross-correlation of EEG signals in the timedomain is envisioned to be within the scope of the present invention.

[0014] It is also envisioned that appropriate selection (i.e., location)of electrode sites can be used to enhance the reliability for detectionand termination of a neurological event. Thus, the present inventionenvisions enhancement of detection by the use of the spatial domain asit applies to the positioning of detection and treatment electrodes.

[0015] Finally, the present invention also envisions signal-to-noiseenhancement for optimizing the detection of neurological events bysearching for signals in a particular frequency domain. For example, alow-pass filter that excludes signals above 5 Hz could be used toenhance the reliability for detection of a neurological event forcertain patients. In addition, detection may be enhanced by firstconditioning the EEG signals using programmable, multiple step, signalprocessing. The processing steps that are envisioned for this signalconditioning include signal summing, squaring, subtracting, amplifying,and filtering.

[0016] It is also envisioned that any combination of techniques forsignal detection in the time, spatial or frequency domain could be usedfor providing a highly reliable system for the detection of aneurological event.

[0017] The present invention envisions four different modalities forstopping the progression of a neurological event such as an epilepticseizure once it has been detected. A preferred method is to provide aresponsive stimulation electrical signal, a second method is to releasemedication in response to the detection of an event, a third method isto provide an electrical short circuit in the vicinity of the epilepticfocus to prevent the occurrence of a full epileptic seizure and a fourthmethod is the application of a sensory input through normal sensorypathways. Such sensory input could be acoustic (sound input), visual(light input), or other sensory input such as mechanical vibration orelectrical stimulation of the skin. Of course it is envisioned that anytwo or more of these modalities can be used in combination in order topreclude, prevent or decrease the severity of a neurological event suchas an epileptic seizure, migraine headache, Parkinson's disease tremor,etc.

[0018] A valuable attribute of the present invention is the ability torecord the EEG signal from any one or all of the detection electrodes.Typically the EEG signal would be continuously recorded in a first-infirst-out (FIFO) digital data recording system where the current dataover-writes the oldest data as memory storage capacity is exceeded. Inthe event that a neurological event was detected, the device would savethe preceding several minutes of data while continuing to recordsubsequent EEG data after the application of a response such asresponsive stimulation, short circuiting of some electrode(s) or thedelivery of a bolus of medication. It is conceived that the device wouldhold in memory the recording made for several minutes both before andafter the neurological event. These data would then be read out by thepatient's physician on a regular basis; e.g., every three months or morefrequently if the device did not promptly terminate some neurologicalevent. It is also anticipated that the patient could use a patient'sinitiating device to trigger the retention of several minutes of datarecording of the EEG signal from a pre-selected group of electrodes.

[0019] It is also conceived that certain other data be recorded that canbe helpful to the physician for treating the patient. These additionaldata would include: (1) the number of neurological events detected sincethe last memory readout and; (2) the number of responses triggered bythe neurological events that were delivered to the patient. Furthermore,the system can be programmed so that when a neurological event isdetected, the electrical signal from any one or more of the multiplesteps in the signal conditioning can be stored in a digital memory.Additionally, telemetry would be provided to the physician that wouldindicate the serial number of the device that is implanted in thepatient and the date and time that each neurological event or patientinitiated recording occurred.

[0020] Another valuable attribute of the present invention is thecapability to program the functions and parameters of the system toenhance the detection of a neurological event and to optimize the systemresponses for stopping a neurological event such as an epilepticseizure. Examples of programmable functions and parameters are: (1) thetime delay introduced for a signal being received from a specificelectrode; (2) the use or non-use of a specific electrode; (3) thefrequency response characteristic of the channel assigned to process thesignal received from a specific electrode; (4) whether or not aparticular electrode is electrically shorted to another electrode or tothe metal case of the device after a neurological event has beendetected; (5) the amplitude, frequency, duration, phase and wave-form ofthe response signal delivered to a specific electrode; (6) theallocation of memory for storing EEG signals as received from one ormore electrodes; (7) determination as to whether or not the data from aparticular electrode will be stored in memory; (8) the amplitude,frequency and time duration of an acoustic, visual, or other sensoryinput applied to the patient in response to the detection of aneurological event, and (9) the specification of statistical data(histograms) to be recorded; for example, the number of epilepticseizures and/or the number of responsive stimulations delivered sincethe last memory readout by an attending physician. These are some butnot all of the programmable functions and parameters that the systemmight utilize.

[0021] It should be understood that a telemetry signal would betransmitted from the implanted device. External receiving equipmenttypically located in the physician's office, would process that signaland provide a paper print-out and a CRT display to indicate the state towhich all the parameters of the implanted device have been programmed.For example, the display would indicate which electrodes are active,what algorithm is being used for detection, what specific bandwidth isbeing used with a specific electrode, etc.

[0022] It should be understood that, unlike implantable automatic heartdefibrillators which generate a responsive signal only after ventricularfibrillation has occurred, it is a goal of the present invention toprevent full development of an epileptic seizure or migraine headachebefore the actual occurrence of such an unwanted neurological event. Inthis regard, the present invention is entirely different from anyimplantable medical device (such as an automatic heart defibrillator)that always allows the unwanted event to occur.

[0023] A specific capability of this system is to provide electricalstimulation to a specific portion of the brain as the means of stoppinga neurological event. It is believed that the earliest possibledetection of a seizure and treatment of aberrant electrical activityfrom an epileptic focus has the highest probability of aborting theoccurrence of a full seizure. It is envisioned that either throughspecific placement of treatment electrodes or by adjusting the phase ofsignals applied to an array of electrodes, stimulation can be directedto the location(s) within the brain that offer the highest probabilityof stopping the seizure.

[0024] It is believed that there is minimal or no effect if a responsivestimulation is produced from an erroneously identified event, i.e., afalse positive. On the other hand, failure to identify a real event ishighly undesirable and could cause the patient to undergo a severeseizure. Therefore, the design concept of the current invention is topredispose the decision making algorithm to never miss a real eventwhile allowing a false positive rate to be detected at up to 5 times therate of actual events.

[0025] Telemetry data transmitted from the implanted device can be sentto a physician's workstation in the physician's office either with thepatient in the physician's office or remotely from the patient's home bymeans of a modem. The physician's workstation can also be used tospecify all of the programmable parameters of the implanted system.

[0026] A novel aspect of a preferred embodiment of this invention isthat the entire implantable portion of this system for treatingneurological disorders lies under the patient's scalp. Such placementwill either have the device located between the scalp and the cranium orthe within a hole in the cranium. Because of size constraints, theintracranial location is the preferred embodiment.

[0027] The implantable portion of the system includes; (1) electrodesthat lie in close proximity to or actually within the brain; (2) acontrol module that contains a battery and all the electronics forsensing, recording and controlling brain activity, (3) electricallyconducting wires that connect the control module to the electrodes, (4)a buzzer providing an acoustic signal or electrical “tickle” indicatingthat a neurological event has been detected, and (5) an input-outputwire coil (or antenna) used for communication of the implanted systemwith any and all external equipment. The battery that provides power forthe system and an electronics module are both contained within a metalshell that lies under the patient's scalp. The metal shell whichcontains the electronics module and the battery collectively form thecontrol module.

[0028] All electrodes connect by means of electrically conducting wiresto electrical terminals that are formed into the metal shell. Theelectronics module is electrically joined to the brain electrodes bymeans of the shell's electrical terminals which are electrically joinedto the wires that connect to the brain electrodes.

[0029] An important aspect of the preferred embodiment of this device isthe fact that the shell containing the electronics module and thebattery, i.e. the control module, is to be placed in the cranium of theskull at a place where a significant volume of bone is removed. Byplacing the entire system within the cranium, (as opposed to having somewires extending into or through the neck to a control module in thechest) the probability of wire breakage due to repeated wire bending isdrastically reduced. However, the present invention also envisions theplacement in the chest or abdomen of a control module if a large batteryor a large volume electronics module dictates such a large size for thecontrol module that it cannot be conveniently placed within the cranium.Such a thoracic or abdominal placement of a control module would requirewires to be run through the neck.

[0030] The present invention also envisions the utilization of anintracranial system for the treatment of certain diseases withoutplacing wires through the neck. Specifically, an alternative embodimentof the invention envisions the use of electrodes in or on the brain withan intracranial control module used in conjunction with a remotesensor/actuator device. For example, blood pressure could be sensed witha threshold of, let us say 150 mm Hg, and if that pressure was exceeded,a signal transmitted by electrical conduction through the body from theremote sensor/actuator device could be received at the control moduleand that would cause brain stimulation in such a way as to reduce theblood pressure. Conversely, if the brain detects pain and provides asignal detectable by the intracranial system, a signal could be sent byelectrical conduction through the body to a remote sensor/actuatordevice which could provide electrical stimulation to locally stimulate anerve to reduce the perception of that pain. Still another example isthat if the precursor of an epileptic seizure is detected, a remoteactuator could be used to electrically stimulate one or both vagusnerves so as to stop the epileptic seizure from occurring. Such a remotedevice could be located in the trunk of the patient's body.

[0031] Another important aspect of this invention is that acomparatively simple surgical procedure can be used to place the controlmodule just beneath the patient's scalp. A similar simple procedure canbe used to replace either the battery or both the battery and theelectronics module. Specifically, if the hair on the scalp is shaved offat a site directly over where the control module is implanted, anincision can then be made in the scalp through which incision a depletedbattery can be removed and replaced with a new battery, or a moreadvanced electronics module can replace a less capable or failedelectronics module. The incision can then be closed, and when the hairgrows back, the entire implanted system would be cosmeticallyundetectable. A good cosmetic appearance is very important for thepatient's psychological well being.

[0032] The manner in which the control module, the electrodes and theinterconnecting wires are placed beneath the scalp is important for thesuccessful implantation of the entire implantable system. Specifically,the control module is optimally placed in either the left or rightanterior quadrant of the cranium. Because the large sagital sinus veinruns along the anterior-posterior center line of the cranium, it isinadvisable to run epidural wires through that region, and furthermore,it would be inadvisable to place the control module directly over thatmajor vein. Since movement of the jaw causes motions of the scalprelative to the cranium, it is advisable to run the connecting wires forelectrodes that must be placed on the anterior portion of the brain inthe epidural space as opposed to running them between the scalp and thecranium. Since the middle meningeal artery and its branches run withingrooves interior to the posterior section of the cranium, it would beinadvisable to connect to posterior placed electrodes by utilization ofconnecting wires positioned in the epidural space beneath the posteriorportion of the cranium. Therefore, the connecting wires for electrodesto be placed on a posterior portion of the brain's surface are bestlocated beneath the scalp, then through burr holes in the cranium wherethey connect to any electrodes placed in a posterior position on thesurface of the dura mater. Conversely, most of the length of theconnecting wires for electrodes located in the anterior portion of thebrain would be placed in the epidural space. In no case should epiduralwires be passed through the anterior-posterior centerline of the brainwhere the large sagital sinus vein is located.

[0033] An important operational aspect of the implanted system is theuse of an input-output coil formed from many turns of fine wire that isplaced between the scalp and the cranium generally along theanterior-posterior center line of the head. All communication betweenthe external equipment and the implanted system can be accomplished bymagnetic induction through the hair and scalp of the patient. Examplesof these signals are the readout of telemetry from the implanted system,or the changing of some operational parameter of the implanted system bymeans of a command from some piece of external equipment. Furthermore,such an input-output coil can be used to recharge a rechargeable batterythat can be located inside the control module. Since the input-outputcoil can be placed on a posterior portion of the cranium, relativemotion of the scalp and cranium should not be a problem in that region.

[0034] By placing the input-output coil in an appropriate site justbeneath the scalp, the patient can be provided with a cap to be worn onthe head which cap includes a flexible coil that can communicate bymagnetic induction using an alternating magnetic field with theimplanted input-output coil. Such a cap could be placed on the patientin the doctor's office when the doctor wishes to read out storedtelemetry or program one or more new parameters into the implantedsystem. Furthermore, the cap could be used by the patient at home forremote connection to the physicians workstation over telephone linesusing a pair of modems, or the cap could be used to recharge arechargeable battery located in the control module of the implantedsystem.

[0035] Another important aspect of the system is a buzzer that can beimplanted just behind the ear on the outer or inner surface of thecranium or actually within a burr hole within the cranium. If aneurological event is detected, the buzzer can provide an acousticoutput that is detectable by the patient's ear or the buzzer can providean electrical “tickle” signal. The buzzer can be used to indicate to thepatient that a neurological event such as an epileptic seizure is aboutto occur so that an appropriate action can be taken. Among theappropriate actions that could be taken by the patient is theapplication of an acoustic, visual or sensory input that could bythemselves be a means for stopping a neurological event such as anepileptic seizure. The acoustic input could be by means of a soundproducing, hearing aid shaped device that can emit an appropriate toneas to pitch and volume directly into the ear. The visual device could befrom a light emitting diode in eyeglasses or a small flashlight type ofdevice that emits a particular type of light at some appropriateflashing rate. A sensory input could be provided by, for example, anexternally mounted electrical stimulator placed on the wrist tostimulate the median nerve or by a mechanical vibrator applied to thepatient's skin.

[0036] When any such acoustic, visual or other sensory input isactuated, either automatically or manually in response to the detectionof a neurological event, literally billions of neurons are recruitedwithin the brain. The activation of these neurons can be an effectivemeans for stopping an epileptic seizure.

[0037] An alternative embodiment of the present invention envisions theuse of a control module located external to the patient's body connectedto electrodes either external or internal to the patient's scalp. Suchan externally located control module might be positioned behind thepatient's ear like a hearing aid.

[0038] Thus it is an object of this invention to provide appropriatestimulation of the human brain in response to a detected neurologicevent in order to cause the cessation of that neurologic event.

[0039] Another object of this invention is to provide increasedreliability for neurological event detection by the use ofcross-correlated signals from multiple electrodes with appropriate timedelay(s) to increase the sensitivity and reliability for detection froma specific area of the brain.

[0040] Still another object of this invention is to exploit a spectralcharacteristic of the signals from multiple electrodes to optimize thedetection of a neurological event.

[0041] Still another object of this invention is to predispose thedecision-making algorithm to allow false positives to cause a responsivestimulation but to disallow missing an actual event.

[0042] Still another object of this invention is to have the response toa neurological event be an electrical stimulation that is focused on aspecific area of the brain by variably delaying the stimulation signalsent from each of several stimulation electrodes placed at differentlocations placed in close proximity to the brain or within the brain.

[0043] Still another object of this invention is to have the specificarea of the brain onto which the response is focused be the area fromwhich the event signal was detected.

[0044] Still another object, of this invention is to record (andultimately recover for analysis) the EEG signal(s) from one or moreelectrodes before, during and after a neurological event.

[0045] Still another object of this invention is to provideprogrammability for all-important operating parameters of the device.

[0046] Still another object of this invention is to provide recording ofthe certain functions of the device such as how many neurological eventswere detected and how many times the device responded to suchdetections.

[0047] Still another object of this invention is to use medicationdelivery as the response to a neurological event, either alone or inconjunction with electrical stimulation.

[0048] Still another object of this invention is to utilize implantedelectronic circuitry which is adaptable to changing EEG input signals soas to provide self-adaptation for the detection and/or treatment of aneurological event.

[0049] Still another object of this invention is to have a system ofelectrodes connected by wires to a control module, the entire systembeing placed under the scalp and being essentially contained within thecranium.

[0050] Still another object of this system is to have essentially noflexure of interconnecting wires so as to enhance system reliability.

[0051] Still another object of this invention is to be able to replace adepleted battery within the system's control module by a comparativelysimple and quick surgical procedure.

[0052] Still another object of this invention is to be able to replacean electronics module within the system's control module by acomparatively simple and quick surgical procedure.

[0053] Still another object of this invention is to be able to rechargethe battery in the control module.

[0054] Still another object of this invention is to provide anexternally situated patient's initiating device that can be used by thepatient when he or she senses that a neurological event is about tooccur in order to provide a response for causing the stopping of thatneurological event or in order to initiate the recording of EEG signalsfrom a pre-selected set of electrodes.

[0055] Still another object of this invention is to utilize a remotelylocated sensor/actuator device within the body to detect an abnormalphysiological condition and send an electrical signal with or withoutwires to a control module within the cranium which then responds by anelectrical signal delivered to the brain to treat the abnormalphysiological condition.

[0056] Still another object of this invention is to utilize anintracranial system for sensing some abnormal physiological conditionand then sending an electrical signal with or without wires to a remotesensor/actuator device that is remotely located within the body to carryout some treatment modality.

[0057] Still another object of this invention is to provide a buzzerwhich indicates to the patient that a neurological event has occurred.

[0058] Still another object of this invention is to provide acoustic,visual or other sensory inputs to the patient either automatically ormanually following the detection of a neurological event so as to stopthe neurological event.

[0059] These and other objects and advantages of this invention willbecome apparent to a person of ordinary skill in this art upon carefulreading of the detailed description of this invention including thedrawings as presented herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0060]FIG. 1 is a top view of a human head showing the configuration ofan implantable system for the treatment of neurological disorders as itwould be situated in the human skull.

[0061]FIG. 2 is a block diagram of the implanted and external portionsof the system.

[0062]FIG. 3 is a block diagram illustrating the event detectionsub-system which utilizes digital signal processing techniques that canexploit either or both time and frequency domain information toaccomplish event detection.

[0063]FIG. 4 is a flow chart pertinent to the processing activitycarried on within the programmable digital signal processor which ispart of the event detection sub-system.

[0064]FIG. 5A illustrates the amplitude of the electrical signalreceived at FIFO memory 344A as a function of time.

[0065]FIG. 5B illustrates the amplitude of the electrical signalreceived at FIFO memory 344B as a function of time.

[0066]FIG. 5C illustrates the amplitude of the electrical signalreceived at FIFO memory 344C as a function of time.

[0067]FIG. 5D illustrates the sum of the time delayed signal amplitudesshowing also that the event detection threshold is exceeded at −20milliseconds.

[0068]FIG. 6 illustrates a block diagram for an alternative algorithmfor detection of a neurological event which uses the amplitudedifferences of signals from pairs of electrodes.

[0069]FIG. 7 is a flow chart of the event recording and processing whichis carried on within the event processing microcomputer used for thesecond stage of an event detection sub-system.

[0070]FIG. 8 illustrates the recording of EEG and /or EEG spectrumsignals by the central processor.

[0071]FIG. 9 shows a flow chart of the central processor function for:(1) receiving event detection information from the event detectionsub-system; (2) sending delay and threshold parameters to the eventprocessing microcomputer and digital signal processor; (3) storing eventrelated data; (4) inducing responsive brain stimulation through thestimulation sub-system; and (5) communicating externally for physiciandata read out and system programming.

[0072]FIG. 10 is a block diagram of the stimulation sub-system as usedto stimulate the brain responsive to a detected event.

[0073]FIG. 11 is a block diagram of the data communication sub-systemand external data interface.

[0074]FIG. 12 is a block diagram of a hybrid analog/digitalrepresentation of the event detection sub-system using time domaininformation for event detection.

[0075]FIG. 13 is a block diagram of a hybrid analog/digitalrepresentation of the event detection sub-system using frequency domaininformation for event detection.

[0076]FIG. 14 is a block diagram of an implantable system that canrespond to a detected neurological event by infusing medication into thepatient's body.

[0077]FIG. 15 is a top view of a human head showing the arrangement of amultiplicity of electrodes connected by wires to a control module thatis implanted within the cranium.

[0078]FIG. 16 is a side view of a human head showing the arrangement ofone surface and one deep electrode connected by wires that pass througha hole in the cranium and connect to a control module that is implantedwithin the cranium.

[0079]FIG. 17 is a top view of a human head showing the arrangement ofan implanted input-output flat wire coil connected by wires to a controlmodule that is implanted within the cranium.

[0080]FIG. 18 is a side view of a human head showing the arrangement ofthe implanted input-output flat wire coil as it would be used with apatient's initiating device to trigger some operation of the implantedsystem.

[0081]FIG. 19 is a side view of a human head showing the arrangement ofthe implanted input-output coil as it would be used with a cap and withthe physician's external equipment to perform some interaction with theimplanted system.

[0082]FIG. 20 is a top view of the shell of the control module.

[0083]FIG. 21 is a cross section of the cranium showing a control moduleplaced essentially within the cranium within a space where cranium bonehas been removed. The cross section of the shell in FIG. 21 is takenalong the section plane 21-21 of FIG. 20.

[0084]FIG. 22 is a side view of the human head and torso showing analternative embodiment of the present invention using a control moduleimplanted within the chest.

[0085]FIG. 23 is a side view of the human head and torso showing analternative embodiment of the present invention using a control moduleimplanted between the scalp and the cranium, a remote sensor/actuatordevice located within the chest, and external devices for applyingacoustic, visual, or other sensory input to the patient.

[0086]FIG. 24 is a side view of a human head showing alternativecommunication means between the external equipment and an implantedcontrol module and also showing alternative locations for electrodesmounted in close proximity to the patient's brain.

[0087]FIG. 25 is a side view of the human head and torso showing analternative embodiment of the present invention using a control modulelocated external to the patient's body and a remote sensor/actuatordevice located within the chest, and external devices for applyingacoustic, visual, or other sensory input to the patient.

DETAILED DESCRIPTION OF THE DRAWINGS

[0088]FIG. 1 illustrates the configuration of an implantable system 10for the treatment of neurological disorders as it would be situatedunder the scalp of a human head 9 having a control module 20, electrodes15A, 15B, 15C, 15N and 16 with wires 17A, 17B, 17C, 17N and 18 connectedthrough the connector 8 to the control module 20. It is envisioned thatthe control module 20 is permanently implanted into the top of the skullin a location where the skull is fairly thick. It is also envisionedthat the control module 20 could be located in the trunk of thepatient's body like a heart pacemaker with the connecting wires beingrun under the patient's skin. The electrodes 15A, 15B, 15C, 15N and 16would be placed under the cranium and above the dura mater (i.e., placedepidurally) or placed deep into the brain. The connecting wires 17A,17B, 17C, 17N and 18 would be run from the control module 20 underneaththe scalp and then be connected to the electrodes placed beneath thepatient's cranium. Although FIG. 1 shows only 4 active electrodes 15A,15B, 15C, 15N with connecting wires 17A, 17B, 17C, 17N, more than 4active electrodes with connecting wires may be used with the presentinvention. The electrode 16 (having a connecting wire 18) could beconsidered a common or indifferent electrode.

[0089] Throughout the detailed description of the present invention, theterminology “the electrodes 15A through 15N” is meant to include allelectrodes 15A, 15B, 15C, . . . to 15N inclusive where N may be anyinteger between 1 and 200. Similar terminology using the words “through”or “to” for other groups of objects (i.e., wires 17A through 17N) willhave a similar inclusive meaning.

[0090] Throughout FIGS. 1 through 25 inclusive, lines connecting boxeson block diagrams or on software flow charts will each be labeled withan element number. Lines without arrows between boxes and/or solidcircles indicate a single wire.

[0091] Lines with arrows connecting boxes or circles are used torepresent any of the following:

[0092] 1. A physical connection, namely a wire or group of wires (databus) over which analog or digital signals may be sent.

[0093] 2. A data stream sent from one hardware element to another. Datastreams include messages, analog or digital signals, commands, EEGinformation, and software downloads to change system operation andparameters.

[0094] 3. A transfer of information between software modules. Suchtransfers include software subroutine calls with and without the passingof parameters, and the reading and writing of memory locations.

[0095] In each case, the text will indicate the use of the line with anarrow.

[0096]FIG. 2 is a block diagram of the implantable system 10 and theexternal equipment 11. The wires 17A through 17N from the electrodes 15Athrough 15N, and the wire 18 from the common electrode 16, are shownconnected to both the event detection sub-system 30 and the stimulationsub-system 40. It is also envisioned to use the case of the controlmodule 20 of FIG. 1 as the common (or indifferent) electrode 16. Thewires 17A through 17N carry EEG signals 21A through 21N from theelectrodes 15A through 15N to the event detection sub-system 30. Theelectrodes 15A through 15N can be energized by the stimulationsub-system 40 via the wires 17A through 17N to electrically stimulatethe patient's brain using the stimulation signals 412A through 412Nrespectively. Although the electrodes 15A through 15N and 16 shown hereare connected to both the event detection sub-system 30 and thestimulation sub-system 40, it is obvious that a separate set ofelectrodes and associated wires could be used with each sub-system.Furthermore, it is envisioned that any one, several or all of theelectrodes 15A through 15N could be electrically connected (i.e.,shorted) to the electrode 16 or to each other. This would beaccomplished by appropriate switching circuitry in the stimulationsub-system 40.

[0097] The event detection sub-system 30 receives the EEG signals 21Athrough 21N (referenced to system ground 19 connected to the wire 18from the common electrode 16) and processes them to identifyneurological events such as an epileptic seizure or its precursor. Acentral processing system 50 with central processor 51 and memory 55acts to control and coordinate all functions of the implantable system10. The interconnection 52 is used to transmit programming parametersand instructions to the event detection sub-system 30 from the centralprocessing system 50. The interconnection 53 is used to transmit signalsto the central processing system 50 identifying the detection of aneurological event by the event detection sub-system 30. Theinterconnection 53 is also used to transmit EEG and other related datafor storage in the memory 55.

[0098] When an event is detected by the event detection sub-system 30,the central processor 51 can command the stimulation sub-system 40 viathe interconnection 54 to transmit electrical signals to any one or moreof the electrodes 15A through 15N via the wires 17A through 17N. It isanticipated that, if appropriate electrical signals 412A to 412Ninclusive are transmitted to certain locations in or near the brain, thenormal progression of an epileptic seizure can be aborted. It may alsobe necessary for the stimulation sub-system 40 to temporarily disablethe event detection sub-system 30 via the interconnection 29 whenstimulation is imminent so that the stimulation signals are notinadvertently interpreted as a neurological event by the event detectionsystem 30.

[0099] A power supply 90 provides power to each component of the system10. Power supplies for comparable implantable devices such as heartpacemakers and heart defibrillators are well known in the art ofimplantable electronic devices. Such a power supply typically utilizes aprimary (non-rechargeable) storage battery with an associated d-c to d-cconverter to obtain whatever voltages are required for the implantablesystem 10. However, it should be understood that the power supply coulduse a rechargeable battery that is charged by means of a coil of wire inthe control module 20 that receives energy by magnetic induction from anexternal coil that is placed outside the patient but in close proximityto the control module. The implanted coil of wire could also be locatedremotely from control module 20 but joined to it by electrical wires.Such technology is well known from the rechargeable cardiac pacemaker.Furthermore, the same pair of coils of wire could be used to providepower to the implanted system 10 when it is desired to read out storedtelemetry or reprogram some portion of the implanted system 10.

[0100] Data stored in the memory 55 can be retrieved by the patient'sphysician by a wireless communication link 72 with the datacommunication sub-system 60 connected to the central processing system50. An external data interface 70 can be directly connected with anRS-232 type serial connection 74 to the physician's workstation 80.Alternately, the serial connection may be via modems 85 and 750 andphone line 75 from the patient's home to the physician's workstation 80.The software in the computer section of the physician's work station 80allows the physician to read out a history of events detected includingEEG information both before, during and after the event as well asspecific information relating to the detection of the event such as thetime evolving energy spectrum of the patient's EEG. The workstation 80also allows the physician to specify or alter the programmableparameters of the implantable system 10.

[0101] As shown in FIGS. 1 and 2, a buzzer 95 connected to the centralprocessor 51 via the link 92 can be used to notify the patient that anevent has occurred or that the implanted system 10 is not functioningproperly. The buzzer could provide a mechanical vibration (typically anacoustic signal) or an electrical stimulation “tickle” either of whichcould be perceived by the patient. By placing the buzzer 95 near the earand on the top of, below, or within a burr hole in the cranium, anacoustic signal emitted by the buzzer 95 will be detectable by thepatient's ear. This sound by itself can be an automatic means forstopping an epileptic seizure.

[0102] A real time clock 91 is used for timing and synchronizing variousportions of the implanted system 10 and also to enable the system toprovide the exact date and time corresponding to each neurological eventthat is detected by the implantable system 10 and recorded in memory.The interconnection 96 is used to send data from the central processor51 to the real time clock 91 in order to set the correct date and timein the clock 91.

[0103] The various interconnections between sub-systems (e.g., theinterconnections 52, 53, 54, 56, 57, 92, 93 and 96) may be either analogor digital, single wire or multiple wires (a “data bus”).

[0104] The operation of the system 10 of FIG. 2 for detecting andtreating a neurological event such as an epileptic seizure would be asfollows:

[0105] 1. The event detection sub-system 30 continuously processes theEEG signals 21A through 21N carried by the wires 17A through 17N fromthe N electrodes 15A through 15N.

[0106] 2. When an event is detected, the event detection sub-system 30notifies the central processor 51 via the link 53 that an event hasoccurred.

[0107] 3. The central processor 51 then triggers the stimulationsub-system 40 via the link 54 to electrically stimulate the patient'sbrain (or electrically short some electrodes or release medication) inorder to stop the neurological event using any one, several or all ofthe electrodes 15A through 15N.

[0108] 4. The stimulation sub-system 40 also sends a signal via the link29 to the event detection sub-system 30 to disable event detectionduring stimulation to avoid an undesired input into the event detectionsub-system 30.

[0109] 5. The central processor system 50 will store EEG signals andevent related data received from the event detection sub-system 30 viathe link 53 over a time from X minutes before the event to Y minutesafter the event for later analysis by the patient's physician. The valueof X and Y may be set from as little as 0.1 minutes to as long as 30minutes.

[0110] 6. The central processor 51 may “buzz” to notify the patient thatan event has occurred by sending a signal via the link 92 to the buzzer95.

[0111]FIG. 3 is a block diagram illustrating an implementation of theevent detection sub-system 30 using digital signal processingtechniques. The event detection sub-system 30 can use either or both,time and frequency domain information for event detection. The eventdetection sub-system 30 receives the signals 21A through 21N from thewires 17A through 17N and processes them to identify the early stages ofa neurological event such as an epileptic seizure. The signals 21Athrough 21N are amplified by the amplifiers 32A through 32Nrespectively, to produce the amplified EEG signals 22A through 22N. Theamplifiers 32A through 32N can also provide low pass and/or high passfiltering to remove unwanted noise. Each amplifier 32A through 32N canbe disabled by a signal placed on interconnection 29 from thestimulation sub-system 40 during brain stimulation so as to preventoverloading the amplifiers or creating an undesired input signal intothe event detection sub-system 30.

[0112] The amplified EEG signals 22A through 22N are then digitized bythe analog-to-digital converters 33A through 33N producing the digitizedEEG signals 23A through 23N which are processed by the programmabledigital signal processor 34 with associated memory 35 to enhance thesignal-to-noise ratio for the detection of neurological events.Processed signals 24 are then passed to the event processingmicrocomputer 36 with associated memory 37 for analysis with the goal ofachieving event detection. When the event processing microcomputer 36identifies an event, it produces a detection signal which it sends alongwith stored EEG and EEG energy spectral data streams to the centralprocessor 51 through the interconnection 53. The central processor 51can pass specific program parameters and revised programminginstructions to the event processing microcomputer 36 via theinterconnection 52. The event processing microcomputer 36 can also passany appropriate program parameters and revised programming instructionsreceived from the central processor 51 on to the programmable digitalsignal processor 34 via the interconnection 25. This scheme providespatient-specific optimization of event detection algorithm(s). Forexample the program might look at signal amplitude differences betweencertain electrodes, or alternately, event detection might be based onanalysis of a signal created by adding the signals (possibly withvarying time delays) derived from a specific subset of the electrodes.It is also possible that the programmable digital signal processor 34might be programmed to perform both digital signal processing and eventprocessing thus not requiring a separate event processing microcomputer36. It is also envisioned that the event processing microcomputer 36 andthe central processor 51 may be the same microcomputer having separatesubroutines in software for each function.

[0113] The amplifiers 32A through 32N, the analog-to-digital converters33A through 33N and the programmable digital signal processor 34 eachseparately and collectively constitute a signal conditioning means forprocessing the EEG signals 21A through 21N. The event processingmicrocomputer 36 provides event detection means for the detection of aneurological event.

[0114] Integrated circuit amplifiers, analog-to digital converters,digital signal processors (DSPs), digital memory and microcomputers andthe techniques to interconnect and program them are well known in theart. Custom VLSI or hybrid circuits could be developed that wouldcombine certain functions.

[0115]FIG. 4 is a flow chart pertinent to the processing activity 340carried on within the programmable, digital signal processor 34 of theevent detection sub-system 30. The digitized EEG signals 23A through 23Nare first processed by the step of removing any d-c bias by thesubroutines 341A through 341N producing digital signals 351A through351N which are then processed by the automatic gain control (AGC)subroutines 342A through 342N to produce the AGC EEG signals 352Athrough 352N. These AGC EEG signals 352A through 352N would then be freeof any d-c bias, and be of identical maximum amplitude during that timewhen the brain is not experiencing a neurological event. The purpose ofAGC is to remove the variation in EEG signal amplitude which can changeslowly over a period of a few hours. Thus the AGC subroutines 342Athrough 342N might adjust the amplitude of incoming signals 351A through351N based on the average energy detected over a period of severalminutes. However, a rapidly changing signal such as that from aneurological event would not have their amplitudes modified by the AGCsubroutines 342A through 342N.

[0116] Using the step of AGC at this stage of the processing will allowthe use of a constant threshold for event identification at a laterstage. The AGC time constant is among the programmable parameters thatcan be programmed in the DSP program instructions 348 that are passedvia the interconnection 25 from the event processing microcomputer 36.AGC algorithms which adjust the output gain based on time averagedenergy are well known in the art and can be implemented by anexperienced DSP programmer. It is also envisioned that the amplifiers32A through 32N of FIG. 3 might be analog AGC amplifiers so that a DSPAGC algorithm would be unnecessary. AGC is an example of a self-adaptivealgorithm used by the event detection subsystem 30.

[0117] The processed EEG signals 352A through 352N are continuouslypassed via the interconnections 24 to the event processing microcomputer36 so that they may be stored for later physician analysis if aneurological event occurs. The processed EEG signals 352A through 352Nare also processed further by additional signal conditioning steps toenhance event identification. These steps involve first squaring thesignals 352A through 352N using the squaring subroutines 343A through343N to produce the squared EEG signals 353A through 353N. The squaredEEG signals 353A through 353N are fed into the First-In-First-Out (FIFO)buffers 344A through 344N where between 1 and 100 milliseconds of datacan be stored. Implementing FIFO data storage in DSP software is wellknown and can be implemented by an experienced DSP programmer.

[0118] Epileptic seizures and many other neurological events canoriginate in a comparatively small section of the brain called anepileptic focus. A preferred embodiment of the digital signal processingalgorithm 340 for event detection is based on the principle that thesignals arriving at the electrodes 15A through 15N (shown in FIG. 2)from an epileptic focus will always do so with essentially the same timedelay for each electrode. Or stated another way, the propagation timerequired for a signal to travel from the epileptic focus to an electrodewill be consistently as follows: t₁ milliseconds for a electrode 15A, t₂milliseconds for electrode 15B, t₃ milliseconds for electrode 15C, etc.,where t₁, t₂, t_(3 . . .) do not significantly change in value fromtime-to-time. The FIFOs 344A through 344N are nothing more than adigital equivalent of a delay line where the sum with delay algorithm345 can elect to sample the squared EEG signals 353A through 353N witheach delayed appropriately to create the time synchronized EEG signals354A through 354N which are summed by the sum with delay algorithm 345.The sum with delay algorithm 345 will produce the sum of timesynchronized squared signals 355. EEG signals originating from parts ofthe brain away from the focus will not be synchronized by the algorithm345 whose time delays are set to synchronize EEG signals originating atthe focus. Thus the amplitude of the sum of time synchronized squaredsignals 355 will be much larger for EEG signals originating at thefocus.

[0119] The delays for each of the FIFO buffers are programmed throughthe DSP program instructions 348. The settings for FIFO time delayswould be derived from analysis of recorded EEG signals during eventsfrom a patient having the same electrode configuration to be used forevent detection. Interconnection 25 is the interconnection over whichthe programming instructions 348 are provided by the event processingmicrocomputer 36 to set the time delay parameters for the FIFO buffers.

[0120] The signal 355 can be sent to the event processing microcomputer36 for time domain event detection. The signal 355 can also betransformed into the frequency domain by the transform algorithm 346,which will produce a frequency spectrum that can change with time havingfrequency band signals 356-1, 356-2, 356-3, 356-4 through 356-M whichare the time evolving signals corresponding to a total of M frequencybands (band 1 through band M). The frequency band signals 356-1 through356-M are digital data streams, each representing the energy of thesignal 355 in the corresponding frequency band (band 1 through band M).An example of such frequency bands is as follows: (a) band 1:1 to 2 Hz;(b) band 2:2 to 4 Hz; (c) band 3:4 to 8 Hz; etc. The specific divisionof the bands is programmable through the DSP programming instructions348 and may be derived for each patient from analysis of recorded EEGinformation. The frequency band signals 356-1 through 356-M are sent tothe event processing microcomputer 36 for the purpose of eventdetection.

[0121]FIGS. 3 and 4 illustrate one embodiment of a multiple step signalconditioning means for the EEG signals 21A through 21N. The specificsteps used in this embodiment are amplification, analog-to-digitalconversion, adjustment of d-c offset, AGC, squaring, time delaying,summing and frequency transformation. The ability to program theprogrammable digital signal processor 34 to implement any combination ofthese or other steps in any order to enhance event detection for eachpatient is an important aspect of the event detection sub-system 30.

[0122]FIGS. 5A, 5B and 5C show the signal traces for a 3 electrodeimplementation of the present invention with the squared EEG signals353A, 353B and 353C stored in the FIFOs 344A, 344B and 344Crespectively. In this example, the FIFOs 344A, 344B and 344C store 100milliseconds of data consisting of 20 samples each, with each samplebeing the average value for a period of 5 milliseconds of the squaredEEG signals 353A, 353B and 353C. The last data placed in the FIFOs 344A,344B, and 344C correspond to time equals zero, and are the most recentsamples of the squared EEG signals 353A, 353B and 353C.

[0123] During pre-implant data recording and analysis of a patient's EEGdata, the relative delays between EEG signals from an epileptic focusarriving at electrodes 15A, 15B and 15C would be calculated. In thisexample, the electrode 15A from which the data in FIFO 344A originates,is the last to receive the EEG signal from such an event. The time delayparameter 358A for the electrode 15A is therefore set to 0. In thisexample, electrode 15B which is the source of data for FIFO 344B, isknown to receive an event signal 15 ms before electrode 15A thus thetime delay parameter 358B for electrode 15B is set to 15 ms. Similarly,electrode 15C from which the data in FIFO 344C receives an event signal35 ms before electrode 1SA; thus the signal delay parameter 358C forelectrode 15C is set to 35 ms.

[0124] Using the time delay parameters 358A, 358B and 358C, the specificsamples 354A, 354B and 354C (marked with the black arrows 6A, 6B and 6C)are fed into the sum with delay algorithm 345. The sum with delayalgorithm 345 adds these specific FIFO samples together to produce thesignal 355 as shown in FIGS. 4 and 5D. FIG. 5D shows the current sampleof the signal 355 and the last 100 milliseconds of the signal 355created by the sum with delay algorithm 345.

[0125] A simple means to detect, a neurological event using the sum withdelay algorithm 345 with resulting signal 355 is to compare the signal355 with a fixed event detection threshold 369 as shown in FIG. 5D. Thethreshold 369 is exceeded at times 0, −10 ms and −20 ms. Thismethodology can be an effective means for event detection when used inconjunction with the automatic gain control algorithms 342A, 342B and342C as shown in FIG. 4. The automatic gain control has the effect whichis seen in FIGS. 5A through 5C of keeping the samples of the squared EEGsignals below the AGC limits 362A, 362B and 362C which limits areprogrammed into the automatic gain control algorithms 342A, 342B and342C shown in FIG. 4. The AGC subroutines 342A, 342B and 342C mightadjust the amplitude of the EEG signals 352A through 352N based on theaverage energy detected over a period of several minutes so that arapidly changing signal such as that from a neurological event will notbe affected.

[0126] It is also envisioned that the delay parameters 358A, 358B and358C may be self-adaptive so that when an event is detected,post-analysis by the digital signal processor 34 using the data storedin the FIFOs 344A, 344B and 344C can determine if adjusting the delays358B and 358C plus or minus in time would increase or decrease the sumof the time synchronized squared EEG signals 355. If the signal 355increases by a shift of the time delay 358B or 358C, then the delayparameters 358B and 358C could be automatically changed to increase thesensitivity for future event detection. This example of the capabilityto modify it's own operating parameters is an example of self-adaptationof the programmable digital signal processor 34. It is also envisionedthat other programmable components of the system 10 of FIG. 2 other thanthe event detection sub-system 30 may be self-adaptive to be capable ofoptimizing system operability without external commands.

[0127] Although FIGS. 5A-5D show the signals relating to animplementation of the present invention using 3 signal electrodes, thealgorithms described can be applied to any set of 2 or more signalelectrodes.

[0128] It is also envisioned that instead of delaying the signals fromeach electrode to provide time synchronization, the electrodes might beplaced at positions where the time delays from an epileptic focus toeach electrode could be the same. Furthermore, it is envisioned thatinstead of squaring the value of the EEG signal amplitude, which is doneto eliminate a zero average over a certain period of time, the sameobjective could be accomplished by rectification of the EEG signal.

[0129]FIG. 6 shows an embodiment of the present invention in which thedigital signal processor processing 440 based on DSP programinstructions 448 takes the digitized EEG signals 23A, 23B, 23C and 23Dfrom four brain electrodes 15A, 15B, 15C and 15D and creates thedifference signal 424 from signals 23A and 23B using the subtractionalgorithm 434, and the difference signal 425 from signals 23C and 23Dusing the subtraction algorithm 435. The difference signals 424 and 425can then be multiplied by weighting factor algorithms 436 and 437 toadjust for difference in signal level for events arriving at each pairof electrodes. The resulting weighted differential EEG signals 426 and427 are summed by the algorithm 438 to create the summed differentialEEG signal 428. The summed differential EEG signal 428 can then betransformed into a set of frequency band signals 456-1 through 456-M bythe algorithm 446 as previously described with respect to the digitalsignal processing 340 shown in FIG. 4.

[0130] The embodiment of FIG. 6 will work best when the electrode pairs15A-15B and 15C-15D are located in positions that will cause the EEGsignal differences 424 and 425 to be synchronized in time for EEGsignals originating at the focus of a neurological event. It is alsoenvisioned that a programmable delay adjustment, as described for FIG.4, could be implemented here if the time delays for EEG signaldifferences 424 and 425 from a neurological event are not the same.

[0131] The summed differential EEG signal 428, the difference EEGsignals 424 and 425, and the frequency band signals 456-1 through 456-Mcan be sent via interconnection 24 to the event processing microcomputer36 for storage.

[0132] It is also envisioned that instead of digitizing the signal fromeach signal electrode 15A through 15N, with respect to a commonelectrode 16, the input stage could use any one or more pairs of brainelectrodes with no single common electrode.

[0133] The processing 340 of FIG. 4 and 440 of FIG. 6 are examples oftwo different implementations of multiple step signal conditioningprograms which can be run within the programmable digital signalprocessor 34 of FIGS. 2 and 3.

[0134]FIG. 7 shows the software flow chart for event recording andprocessing 360 of the event processing microcomputer 36 used for thesecond stage of the event detection sub-system 30 shown in FIGS. 2 and3. Specifically, event recording and processing 360 represents thealgorithms and subroutines in software used by the event processingmicrocomputer 36 (hardware) as the event detection means and also torecord relevant EEG and spectral band data. A primary objective of eventrecording and processing 360 software is to make possible the recordingof AGC modified EEG signals 352A through 352N inclusive and thefrequency band signals 356-1 to 356-M inclusive by the centralprocessing system 50.

[0135]FIG. 8 indicates that the central processing system 50 is capableof recording EEG and frequency band data for “X” minutes before aneurological event is detected and “Y” minutes after the neurologicalevent is detected. The event recording and processing 360 of FIG. 7 isused to facilitate this data recording capability. Specifically, the EEGsignals 352A through 352N (also see FIG. 4) are stored in data FIFOmemories 363A through 363N. If an event is detected, the FIFOs 363Athrough 363N can be read by the central processor 51 via the link 53 toretrieve the stored EEG data streams 373A through 373N for a time “X”minutes before the event. The central processor 51 can also read thedata FIFOs 363A through 363N in real time after detection of aneurological event for a period of “Y” minutes. Alternatively the dataFIFOs 363A through 363N could be used to store and then read out “Y”minutes of data stored after the event is detected. In either case, thegoal of retrieving “X” minutes of pre-event detection data and “Y”minutes of post-event detection data (as indicated in FIG. 8) can beachieved. It should be remembered that if there are N electrodes thenthere will be as many as N channels of AGC modified EEG data that can berecorded. However, the central processing system 50 may be programmed torecord EEG data from a sub-set of the electrodes 15A through 15N (seeFIG. 2). All data stored by the central processing system 50 can beretrieved by the patient's doctor for analysis with the goal ofimproving the response of the system 10 so as to more reliably stop aneurological event.

[0136]FIG. 7 also shows two different schemes for detecting an event. Ifthe amplitude of the sum of the time synchronized squared EEG signals355 exceeds the event detection threshold 369 as shown in FIG. 5D (usingthreshold detector algorithm 368 of FIG. 7), the algorithm 368 sends apositive event detected message 358 to the event densitycounter/detector algorithm 371. The event density counter/detectoralgorithm 371 determines if there have been enough events in the mostrecent time period “T” to notify the central processor 51 with the eventidentified message 372 indicating that an event has really occurred. Atypical time period “T” would be approximately 2 seconds but could be inthe range from ½ to 100 seconds. The event density counter/detectoralgorithm 371 will reduce the number of false positive eventidentifications by eliminating short uncorrelated EEG bursts. If thenumber of events in the time period “T” is set equal to 1, then thesystem will be most sensitive and any time sample which exceeds thethreshold 369 in the threshold detector algorithm 368, will be passed onas an event identified message 372. A typical setting for the number ofevents for a two second time period “T” would be four.

[0137] The system for detecting a neurological event based on thethreshold detector 368 would involve processing data for the entirefrequency spectrum of the sum of the time synchronized and squared EEGsignals 355. As shown in FIG. 4 the signal 355 can be transformed into aset of frequency band signals 356-1 through 356-M inclusive each ofwhich signals is of limited bandwidth as compared with the broadbandsignal 355. Each of the frequency band signals 356-1 through 356-M ofFIG. 7 can be analyzed by a threshold detector algorithm 367-1 through367-M respectively in a manner exactly analogous to the thresholddetector algorithm 368 used to detect events from the broadband signal355.

[0138] In a manner analogous to the threshold detector algorithm 368,each of the set of threshold detector algorithms 367-1 through 367-M cansend a positive event detected signal 357-1 through 357-M to acorresponding frequency band event density counter/detector 369-1through 369-M when the amplitude of the frequency band signal 356-1through 356-M exceeds a preset threshold level. The frequency band eventdensity counter/detectors 369-1 through 369-M will, analogous to theevent density counter/detector 371, determine if there are a sufficientnumber of events per time period “T” in any of the bands 1 through M tosend an event identified message 359-1 through 359-M to the centralprocessor 51 indicating that a neurological event has occurred.

[0139] Analogous to the storage of the AGC modified EEG signals 352Athrough 352N by the data FIFOs 363A through 363N, each of the Mfrequency band signals 356-1 through 356-M is stored in FIFO memories366-1 through 366-M, so that if an event is detected, the FIFOs can beread by the central processing system 50 via the link 53 to retrieve thefrequency band data streams 376-1 through 376-M for a time “X” beforeevent detection until some time “Y” after event detection. As previouslydescribed, FIG. 8 illustrates this concept for data storage.

[0140] Constructing computer code to store and retrieve sampled digitalsignals from FIFO memory is well known in the art of software design.Comparing an input signal amplitude against a preset threshold,determining the number of counts per unit time and comparing the countsper unit time against a preset number of counts per unit time are alsowell known in the art of software design.

[0141] It should be understood that the software which is the digitalsignal processor processing 340 (see FIG. 4) is run by the programmabledigital signal processor 34 according to the DSP program instructions348. In a similar manner, the software for event recording andprocessing 360 (see FIG. 7) is run by the event processing microcomputer36 of FIG. 4 according to the program instructions for DSP and eventprocessing 375. Additionally the programming instructions for DSP andevent processing 375 serves as a pass through for the DSP programinstructions 348 of FIG. 4. The program instructions for DSP and eventprocessing 375 are received by the event processing microcomputer 36(using the software for event recording and processing 360) from thecentral processor 51 via the interconnection 52. The DSP programinstructions 348 (see FIG. 4) are received over interconnection 25 bythe digital signal processor 34 from the program instructions for DSPprocessing and event processing 375 of FIG. 7.

[0142] The thresholds to be used for detection by the threshold detectoralgorithms 368 and 367-1 through 367-M and the required event densitiesfor event identification by the event density counter/detectoralgorithms 371 and 369-1 through 369-M, will typically be programmed tominimize the chance of missing a “real” neurological event even thoughthis could result in the occasional false positive identification of anevent. This bias toward allowing false positives might typically be setto produce from ½ to 5 times as many false positives as “real” events.

[0143] It is also envisioned that the software for event recording andprocessing 360 might not require a separate microcomputer but couldoperate either as a set of subroutines in the central processor 51 or aset of subroutines in the programmable digital signal processor 34.

[0144] It is also envisioned that the event recording and processingsoftware 360 could be programmed to provide an event detection meansbased on detecting specific aspects of the waveform of either time orfrequency domain outputs of the signal conditioning by the digitalsignal processor 36. Such aspects of the waveform could include pulsewidth, first derivative or waveform shape.

[0145]FIG. 9 shows a flow chart of the software for central processorprocessing 510 as run by the central processor 51 of FIG. 2. The centralprocessor 51 receives event detection messages 372 and 359-1 through359-M, EEG data streams 373A through 373N and the frequency band datastreams 376-1 through 376-M from the event processing microcomputer 36.The central processor 51 of FIG. 2 also sends and receives data to andfrom the data communication sub-system 60 via interconnections 56 and57. The processing 510 processes these messages, signals, and datastreams.

[0146] Algorithm 514 receives the event detection messages 372 and 359-1through 359-M provided by the event processing microcomputer 36 via thelink 53. When the algorithm 514 receives such a message indicating thata neurological event has occurred, the algorithm 514 calls thesubroutine 512. The calling of the subroutine 512 by the algorithm 514is indicated by the element 515. The subroutine 512 reads and saves tothe central processor's memory 55 via the link 518, the last X minutesof stored EEG data streams 373A through 373N and frequency band datastreams 376-1 through 376-M from the event processing microcomputer 36.The algorithm 512 will continue to read and save to the centralprocessor's memory 55, the next “Y” minutes of EEG data streams 373Athrough 373N and frequency band data streams 376-1 through 376-M fromthe event processing microcomputer 36. As seen in FIG. 8, these datastreams may include a blank period during stimulation followed by datawhich can be analyzed to determine the efficacy of the treatment. Thealgorithm 514 also causes a signal 511 to be sent to the stimulationsub-system 40 via the link 54 to cause the stimulation sub-system 40 torespond as programmed to stop, the neurological event.

[0147] Values for X and Y will typically be several minutes for X and asmuch as a half-hour for Y. The memory 55 must be large enough for atleast one event and could be large enough to hold 10 or more events. Thevalues X and Y like other parameters are programmable and adaptable tothe needs of each particular patient.

[0148] The I/O subroutine 517 receives physician commands from the datacommunication sub-system 60 via the link 56 and, in turn, reads andsends back via the link 57 the data stream 519 containing the eventrelated data previously stored in the memory 55 by the algorithm 512.These data are transmitted to the external equipment 11 by the datacommunication sub-system 60 via the wireless link 72 as shown in FIGS. 2and 11.

[0149] The I/O subroutine 517 also plays a key role in the downloadingof software programs and parameters 59 to the programmable sub-systemsof the implantable system 10 of FIG. 2. These programmable sub-systemsinclude the event detection sub-system 30, the central processing system50 and the stimulation sub-system 40. The programmable components of theevent detection sub-system 30 are the programmable digital signalprocessor 34 and the event processing microcomputer 36 shown in FIG. 3.The programming instructions and parameters 59 for the programmablesub-systems 30, 40 and 50 are downloaded through the I/O subroutine 517by the programming and parameters downloading subroutine 516 of thecentral processor processing 510. The subroutine 516 stores theinstructions and parameters 59 and downloads the program instructionsfor DSP and event processing 375 (also see FIG. 7) for the eventdetection sub-system 30 via link 52 to the event processingmicrocomputer 36. The subroutine 516 also downloads the stimulationsub-system instructions and parameters 592 via the link 54 to thestimulation sub-system 40. The subroutine 516 also updates the memory 55with the programming instructions and parameters 594 for the centralprocessor processing 510.

[0150] Programmable microprocessors or self-contained microcomputers,such as the Intel 8048 and 8051, which contain read only memory forbasic programs and random access memory for data storage and/or programstorage, can be used to implement the central processor processing 510as previously described. It is also envisioned that a custom VLSI chipinvolving microprocessor, signaling and memory modules could be producedspecifically for this application. All of the previously describedalgorithms to store data, send notification signals and messages andmake decisions based on input data are straightforward for a softwareprogrammer to implement based on the current state of the art.

[0151] It is also clear that current memory technology should besuitable for EEG storage. For example, the EEG storage for a 4 electrodesystem using 8 bits (one byte) per sample at a sampling rate of 250samples per second (required for frequencies up to 125 Hz) will require60,000 bytes per minute of data storage. Having 100 minutes of storagewould require only 6 megabytes, which is readily achievable usingcurrent memory chip technology. Thus if both X and Y were each 1 minute,then a total of 50 neurological events could be stored in the 6 megabytememory.

[0152] It is also envisioned that with well known data compressiontechniques such as adaptive pulse code modulation, the memoryrequirements can be reduced significantly.

[0153] It should be understood that instead of using random accessmemory to store the EEG data, non- volatile memory such as “flashmemory” could be used to conserve power.

[0154]FIG. 10 illustrates the stimulation sub-system 40 including itsinterconnections to other sub-systems. The stimulation sub-system 40 isused to stimulate the brain, responsive to a detected event. Thepreferred embodiment of the stimulation sub-system 40 comprises a delayprocessing microcomputer 420 and N signal generators 422A through 422Nattached to the electrodes 15A through 15N by the wires 17A through 17N.The event detection signal 511 from the central processor 51 is receivedby the delay processing microcomputer 420 which first sends a signal viathe link 29 to the event detection sub-system 30 to shut down eventdetection during stimulation. The delay processing microcomputer 420will then feed stimulation command signals 410A through 410N to thesignal generators 422A through 422N for a specific pre-programmed timeperiod. The stimulation command signals 410A through 410N may besimultaneous or may have a relative delay with respect to each other.These delays can be downloaded by the instruction and parameter download592 from the central processor 51 via the link 54. It may be desirablethat the delays be adjusted so that the stimulation signals 412A through412N from the signal generators 422A through 422N reach the neurologicalevent focus in the brain at the same time and in-phase. This couldenhance performance of the stimulation sub-system 40 in turning off aneurological event. Alternately, experience may indicate that certainsignals being out of phase when they arrive at the neurological eventfocus may be particularly efficacious in aborting a neurological event.

[0155] The stimulation command signals 410A through 410N can be used tocontrol the amplitude, waveform, frequency, phase and time duration ofthe signal generators' output signals.

[0156] The typical stimulation signals 412A through 412N generated bythe signal generators 422A through 422N should be biphasic (that is withequal energy positive and negative of ground) with a typical frequencyof between 30 and 200 Hz, although frequencies of between 0.1 and 1000Hz may be effective. It is also envisioned that pure d-c voltages mightbe used, although they are less desirable. If frequencies above 30 Hzare used, the signal generators could be capacitively coupled to thewires 17A through 17N. The typical width of the biphasic pulse should bebetween 250 and 500 microseconds, although pulse widths of 10microseconds to 10 seconds may be effective for a particular patient.Typical voltages applied may be between 1 millivolt and 10 volts rms.The stimulation would typically be turned on for several secondsalthough times as short as a 1 millisecond or as long as 30 minutes maybe used.

[0157] Biphasic voltage generation circuits are well known in the art ofcircuit design and need not be diagramed here. Similarly, the code tohave the delay processing microcomputer 420 provide different commandparameters to the signal generators 422A through 422N is easilyaccomplished using well known programming techniques.

[0158] Although the delay processing microcomputer 420 is shown here asa separate unit, it may be practical to have the central processor 51 orthe event detection microcomputer 36 of FIG. 3 provide the requiredprocessing. Consolidating many of the processing functions within asingle processor is practical with the system 10 of FIG. 2 as the realtime demands on any one system typically occurs when the others are notextremely busy. For example, during processing to identify an event,there is no need for data I/O, EEG storage or stimulation. When an eventis detected and there is a need for EEG storage and stimulation, thereis reduced need for event detection processing.

[0159] It is also envisioned that the stimulation sub-system 40 couldoperate with only one electrode such as a single electrode centrallylocated at an epileptic focus, or a deep electrode implanted in thethalmus or the hippocampus of the brain. If this were the case, thedelay processing microcomputer 420 would not be needed, and only asingle signal generator circuit would be required. By “located at anepileptic focus” it is meant that the electrode would be placed within 2centimeters of the center of that focus.

[0160]FIG. 11 shows the block diagram of the data communicationsub-system 60 and the external data interface 70 includinginterconnections to the central processor 51 and the physician'swork-station 80. When communication from the physician's workstation 80to the central processor 51 is desired, the antenna 730 of the externaldata interface is placed near the antenna 630 of the data communicationsub-system 60. The workstation 80 is then connected by the cable 74 toan RS-232 serial data interface circuit 740 of the external datainterface 70. The RS-232 serial data interface circuit 740 connects tothe RF transmitter 720 and RF receiver 710 through the serialconnections 722 and 712, respectively. Alternatively, if the patient isremotely located from the physician's workstation 80, the workstation 80can be connected to the RS-232 serial data interface over a dial-upconnection 75 using the modems 750 and 85.

[0161] Once the connection 74 or 75 has been established, wirelesssignals 72 can sent to and from the RF transmitter/receiver pair 610 and620 of the data communication sub-system 60 and the RFtransmitter/receiver pair 710 and 720 of the external data interface 70.The wireless signals 72 are used to command software updates via thelink 612 through the serial-to-parallel data converter 614 and the link56 to the central processor 51. The wireless signals 72 are also used tosend stored data back through the link 57 through the parallel-to-serialdata converter 624 through the link 622 to the RF transmitter 620.

[0162] RF transceiver circuitry and antennas similar to this are used indata communication with heart pacemakers and defibrillators, andtherefore, this technology is well known in the art of implantableprogrammable devices. RS-232 interfaces, serial to parallel and parallelto serial conversion circuits, are also well known.

[0163]FIG. 12 is a block diagram of a hybrid analog/digital embodimentof an event detection sub-system 130 that uses time domain informationfor event detection. In this embodiment, analog circuitry 139 is used toprocess and detect possible neurological events, and digital logiccircuitry 138 is used to check if the density of possible events issufficient to declare a “real” event. As in FIG. 3, the incoming EEGsignals 21A through 21N on wires 17A through 17N are amplified by theamplifiers 131A through 131N which may also provide band-pass orlow-pass filtering and/or AGC of the signals 21A through 21N resultingin the amplified signals 121A through 121N which are then squared by thesquarer circuits 132A through 132N resulting in the squared signals 122Athrough 122N. The squared signals 122A through 122N are then processedby a series of analog delay line circuits 133A through 133N to createthe squared and time synchronized EEG signals 123A through 123N, whichare subsequently added together by the summing circuit 135. Theresulting summed time synchronized signal 125 is then fed into athreshold detection circuit 136 which will output a digital pulse 126whenever the summed time synchronized signal 125 exceeds a pre-setthreshold. The digital pulses 126 collected over time are then processedby the digital logic circuit 138 to determine if the event is real ornot. The delay parameters 124A through 124N are input to the delay lines133A through 133N from the central processor 151 and can be pre-set fora particular patient. Setting the values for these time delays could bebased on measured delays of EEG signals received from an epileptic focusduring diagnostic testing of the patient using the implanted system 10of FIG. 2. During brain stimulation, a signal 129 is sent from thestimulation sub-system 40 to shut down the amplifiers 131A through 131Nto avoid amplifier overload or mistakenly identifying a stimulationsignal as a neurological event signal.

[0164] Analog integrated circuits to multiply or sum analog signals arecommercially available. Integrated circuit bucket brigade analog delaylines are also commercially available. It is also envisioned that ahybrid circuit containing multipliers, summers and delay lines could beproduced to miniaturize the system 130. A standard comparator circuit,also available as an integrated circuit, can be used as the thresholddetector 136 to compare the signal 125 with a pre-set threshold. If thethreshold is exceeded, then a pulse is sent via the connection 126 fromthe threshold detector circuit 136 to the event counter 141 of thedigital logic 138.

[0165] The digital logic 138, which counts the number of event pulsesper second emitted by the threshold detector 136, can be implementedusing a simple programmable microcomputer similar to that described forevent recording and processing 360 shown in FIG. 7, or it can beimplemented by a collection of standard digital logic and countingcircuitry. Such a set of circuitry could use a counter 141 to count thepossible event pulses 126 generated by the threshold detector 136. Anevent detected pulse 128 would be emitted by the counter 141 only whenit overflows. If the counter 141 is reset once a second by a reset pulse147 from an OR gate 146 which has been sent a pulse 144 from the clock142, then only if the counter 141 overflows in the one second timeperiod between reset pulses 147 will the event detected pulse 128 begenerated. Certain available counter chips can be reset to a presetnumber rather than 0. In FIG. 12, the event counter 141 could beimplemented with such a counter chip so that a reset signal will causethe counter to reset to a preset number 148 that would be set via theconnection 145 from the central processor 151. Thus, for example, an 8bit counter (which counts up to the number 256) could be set to overflowwhen the number of pulses counted by the counter 141 causes it to countfrom the downloaded preset number 148 to the number two hundred andfifty-six in less than one second. Of course, times of less than 1second or more than 1 second can also be used for the time between thepulses 144 from the reset clock 142. The event detected pulse 128 isalso used to reset both the clock 142 and the event counter 141. An ORgate 146 will allow the event counter 141 to be reset by either thepulse 144 from the clock 142 or the event detected pulse 128. Theprocessing by the central processor 151 would be analogous to that shownin FIG. 9.

[0166] The specific threshold to be used for detection by the thresholddetector 136 and the preset 148 for the event counter 141 will typicallybe set to minimize the chance of missing a “real” event even though thiswill result in occasional false positive identification of an event.

[0167]FIG. 13 is a block diagram of a hybrid analog/digitalrepresentation of still another embodiment of the event detectionsub-system 230 using frequency domain information for event detection.In this embodiment, analog circuitry 239 is used to process and detectpossible events in each of M frequency bands. Digital logic circuitry238 is used to check if the density of possible events is sufficient todeclare a “real” event. The front end (up through and including the sum135) of the analog circuitry 239 of the sub-system 230 is identical tothe front end of the analog circuitry 139 of FIG. 12. As in FIG. 12, theincoming EEG signals 21A through 21N on wires 17A through 17N areamplified by the amplifiers 131A through 131N. These amplifiers 131Athrough 131N (which may also provide band-pass or low-pass filtering ofthe signals 21A through 21N) produce the amplified signals 121A through121N. The amplified signals 121A through 121N are then squared by thesquarer circuits 132A through 132N resulting in the squared signals 122Athrough 122N. The squared signals 122A through 122N are then processedby a series of analog delay line circuits 133A through 133N to createthe squared and time synchronized EEG signals 123A through 123N, whichare subsequently added together by the summing circuit 135. Theresulting summed time synchronized signal 125 is fed to a set of analogband-pass filters 266-1 through 266-M for the M frequency bands. Theresulting band signals 256-1 through 256-M are examined by the thresholddetectors 267-1 through 267-M analogous to the threshold detector 136 ofFIG. 12. Each of the threshold detectors (267-1 through 267-M) willgenerate a corresponding pulse (257-1 through 257-M) when a presetthreshold is exceeded analogous to the pulse 126 generated by thethreshold detector 136 of FIG. 12. The pulses 257-1 through 257-M arefed into the event density counter/detectors 268-1 through 268-M eachidentical to the digital logic circuit 138 of FIG. 12. The event densitycounter/detectors 268-1 through 268-M will feed the detected frequencyband event pulses 258-1 through 258-M to the central processor 251.

[0168] The central processor 251 processes events from event densitycounter/detectors in a similar manner to the central processor 151 ofFIG. 12. The main differences are that the counter presets 259-1 through259-M may be different for each of the bands as required to optimizesensitivity. During responsive brain stimulation, a signal 129 is sentfrom the stimulation sub-system 40 to shut down the amplifiers 131Athrough 131N to avoid amplifier overload or mistakenly identify astimulation signal as an event signal. The processing by the centralprocessor 251 would be analogous to that shown in FIG. 9.

[0169]FIG. 14 is a diagram of an implantable system 910 which canrespond to a detected neurological event by infusing medication from animplantable medication system 91 into the patient's body through thehollow catheter 93. The system 910 is identical to the system 10 of FIG.2 except that the programmable drug delivery sub-system 91 replaces thestimulation sub-system 40 of FIG. 2 as the sub-system which provides theresponse to an neurological event detected by the event detectionsub-system 30. In this embodiment, the signal indicating that an eventhas been detected and the programming instructions for the implantabledrug delivery system 91 are transmitted via the link 96 from the centralprocessor 51. It may be desirable to place the outlet of the catheter 93into the cerebrospinal fluid (CSF) to provide rapid infusion to allareas of the brain, or it may be desired to have the outlet of thecatheter 93 positioned to deliver medication to one specific location inthe brain or possibly into the bloodstream.

[0170] The operation of the system 910 of FIG. 14 for detecting andtreating a neurological event such as an epileptic seizure is asfollows:

[0171] 1. The event detection sub-system 30 continuously processes theEEG signals 21A through 21N carried by the wires 17A through 17N fromthe N electrodes 15A through 15N.

[0172] 2. When an event is detected, the event detection sub-system 30notifies the central processor 51 via the link 53 that an event hasoccurred.

[0173] 3. The central processor 51 signals the drug delivery system 91via the link 96 to infuse medication through the catheter 93 into thepatient's body as a means for stopping a neurological event.

[0174] 4. The drug delivery system 91 delivers pre-programmed druginfusion to the desired site.

[0175] 5. The central processor 51 will store EEG and event related datafrom X minutes before the event to Y minutes after the event for lateranalysis by the patient's physician.

[0176] 6. The central processor 51 may initiate a “buzz” to notify thepatient that an event has occurred by sending a signal via the link 92to the buzzer 95.

[0177] Programmable implantable drug delivery systems are described insome detail in the Fischell patent 4,373,527. It is also envisioned thatboth electrical stimulation and drug delivery could be used together toimprove the outcome in the treatment of a neurological disorder.

[0178] It should also be understood that although the inventiondescribed herein has been described with analog or digitalimplementations of various aspects of the invention, the invention maycombine analog and digital elements described herein in differentcombinations than as described.

[0179] In addition, although the previous descriptions relate to a fullyimplantable system, an externally worn system with implanted electrodescould function adequately and would allow a plug-in interface to thedata communication sub-system 60 and simple battery replacement. It isalso envisioned that the techniques described above would work with anexternal device with electrodes attached to the outside of the head.External devices would have great merit in determining if an implantablesystem would work well enough to be warranted. An external version withimplanted electrodes could be used to record EEG signals fromneurological events to calculate the optimal programming algorithms andparameters to be used by a permanently implanted system using the sameset of electrodes.

[0180] It is also envisioned that the EEG recording capabilities of thepresent invention could be used without the event detection andstimulation components to store patient EEG activity for diagnosticpurposes.

[0181] Novel arrangements for the physical placement of the variousparts of a system for the treatment of neurological disorders are shownin FIGS. 15 to 25 inclusive. Specifically, FIG. 15 shows a top view ofan intracranial system 600 consisting of brain surface electrodes 601,602, 603, 604, 605 and 606 connected by wires 611, 612, 613, 614, 615and 616 respectively which provide an electrical conducting means tojoin the electrodes 601 through 606 to a control module 620. Thus theproximal end of each of the wires 611 through 616 is connected to thecontrol module 620, and the distal end of each of the wires 611 through616 is connected to an electrode. Inside the patient's head 9, thesesurface electrodes 601-606 are placed between the bottom of the cranium(i.e., inside the skull) and the top of the dura mater that surroundsthe brain. Thus this is an epidural placement of the surface electrodes.Although six surface electrodes are shown in FIG. 15, it is envisionedthat as many as 12 or more active electrodes could be usefullyimplanted. It is further envisioned that the metal case of the controlmodule 620 could serve as a common or indifferent electrode which alsocould be considered to be at ground potential. It is further envisionedthat the control module might utilize a case which is non-conducting inwhich only part of the outer surface is conducting so as to provide oneor more electrodes. Also shown in FIG. 15 is a deep electrode 601Dconnected by wire 611D to the control module 620. It is anticipated thatas many as eight deep electrodes could be used with the intracranialsystem 600. One or more deep electrodes might advantageously be placedin the hippocampus and/or the thalmus or possibly some other portion ofdeep brain tissue.

[0182]FIG. 16 is a simplified side view of the human head 9 into whichthe intracranial system 600 has been implanted. In this simplified view,only one brain surface electrode 602 is shown and one deep electrode601D. The brain surface electrode 602 is connected by the insulated wire612 to control module 620. Also shown in FIG. 16 is the deep electrode601D connected by the wire 611D to the control module 620.

[0183]FIGS. 15 and 16 also show that the control module 620 is locatedin an anterior portion of the patient's head 9. By an anterior portionis meant that it is located anterior to the head's lateral centerline(LCL) that roughly goes through the center of the ears. Furthermore, thecontrol module 620 cannot be situated on the anterior-posteriorcenterline (APCL) because just under the APCL is the very large sagitalsinus vein, and it would be inadvisable to place the control module 620at such a location. The reason for placing the control module 620 in theanterior half of the patient's cranium is that the middle meningealartery and its branches, (which arteries all lie posterior to the LCL)cause grooves to be formed in the underside of the cranium. Therefore,that location is also inappropriate for removing the considerable volumeof cranium bone that should be removed for placement of the controlmodule 620.

[0184]FIGS. 15 and 16 also show that the electrodes are connected bywires to the control module 620 via holes that are made by removing bonefrom the patients cranium. Specifically, the interconnecting wires 611,612, 613 and 614 pass respectively through the holes H1, H2, H3 and H4.It can also be seen in FIG. 15 that the wire 616 passes through the holeH1 and wires 615 and 611D pass through the hole H4. The reason for thismethod of sometimes running most of the wire length between the scalpand the cranium and at other times running most of the wire lengthbetween the bottom of the cranium and the dura mater has to do with themovement of the scalp relative to the cranium which occurs on theanterior portion of the patient's head and also is done to avoid placingthe wires epidurally where the middle meningeal artery and its brancheshave made grooves in the interior surface of the cranium. Specifically,it will be noted that the wires 612 and 613 are placed under the scalpfor most of their length because in this posterior portion of thepatient's head the scalp exhibits very little motion relative to thecranium but the middle meningeal artery and its branches do causeinterior surface grooves in the cranium in this posterior region of thehead. The reverse situation is seen for the connecting wires 615 and616. In this case, because there is considerable motion of the scalprelative to the cranium in the anterior portion of the patient's head,most of the length of the wires 615 and 616 is placed epidurally wherethere are no grooves in the interior surface of the cranium.

[0185] Indicated by phantom lines in FIG. 15 is the location of anepileptic focus 630 where an electrode 601 has been placed. Aspreviously described, it may be advantageous to provide an electricalshort circuit between such an electrode 601 located over the epilepticfocus 630 and the metal case of the control module 620 which acts as anindifferent, common or ground electrode. Also, responsive stimulationusing only the electrode 601 may be sufficient to abort an epilepticseizure with no other electrode being actuated.

[0186]FIG. 17 shows the location of the control module 620 connected bywires 631 and 632 to a flat wire input-output coil 635 that is placed ina posterior position on the patient's head along the APCL.

[0187]FIG. 18 shows a cross section of the patient's cranium along theAPCL showing the cross section of flat wire coil 635 and also shows apatient initiating device 750 having a case 751 and an initiating button752.

[0188]FIG. 19 shows a cross section of the patient's cranium along theAPCL again showing the cross section of the flat wire coil 635 and alsothe cross section of a cap 636 which includes a flat wire input-outputcommunication coil 637. The flat wire coils 635 and 637 can act asemitting and receiving devices to provide two-way communication betweenthe control module 620 and the external equipment 11.

[0189] The flat wire coil 635 serves several important functions for theoperation of the implanted system 10. A first use is as the means tocommunicate by magnetic induction between the external equipment 11 andthe implanted system 600. By “magnetic induction” is meant that analternating magnetic field generated by (for example) the coil 638generates an electrical current in the coil 635. Such an alternatingmagnetic field can also be modulated to provide the wireless two-waycommunication link 72 of FIG. 2. The external equipment 11 via thecommunication coil 637 can be used to read out telemetry stored in thecontrol module 620 or reprogram the control module 620 with new softwareor operational parameters. Another use of the flat coil 635 is to allowthe patient's initiating device 750 to cause a specific action to occurwithin the implanted system 10. For example, the device 750 can be usedto trigger a response from the implanted system 600 that would beinitiated by the patient when he or she feels that some neurologicalevent was about to occur. For example, when the aura of a seizure isfelt or some visual manifestation of a migraine headache, the patientwould place the device 750 over the site of the implanted control moduleand then press the actuate button 752. The device 750 might have severalbuttons to initiate different responses from the implanted system 600.One response that the patient may wish to have accomplished is to holdin memory the prior several minutes of recorded EEG data if the patientfeels that data may be important to an understanding of his neurologicalcondition. Furthermore, the pressing of different buttons could be usedto initiate some different response from the implanted system 600.Specifically, by pressing on the button 752, a coil within the patient'sinitiating device 750 can communicate by magnetic induction with theflat coil 635 to carry out a specific action such as: (1) hold datastored in the FIFOs to be read out at a later time, (2) provide apre-programmed response to stop a neurological event, (3) turn off theimplanted system, and (4) initiate any other action requested by thepatient that has been pre-programmed by the physician. Another use forthe flat coil 635, as shown in FIG. 19, is to connect the communicationcoil 637 via the wire 638 to the charging equipment 639 as required torecharge a rechargeable battery that would be located in the controlmodule 620. The external equipment 11 could also provide electricalpower to the control module 620 during readout of telemetry or duringreading in of new operational parameters. Powering the control module620 from an external source during such times of high power drains couldextend the lifetime of a primary (non-rechargeable) battery located inthe control module 620.

[0190] Although FIG. 17 shows the flat coil 635 located remotely fromthe control module 620, such a coil could also be placed on the surfaceof or interior to the control module 620. Remote placement has theadvantage that the high frequency and intense alternating magnetic fieldrequired for communication or recharging would not be placed onto theelectronics portion of the control module 620 thus avoiding interferencewith the operation of the system 600. The coupling by magnetic inductionof the coil 635 with either the device 750 or the communication coil637can provide the wireless communication link 72 of FIG. 2. It isenvisioned that any of the two-way communication capabilities describedherein could be implemented with either the electromagnetic inductionstructures as shown in FIGS. 17, 18 and 19 or by the radio frequency(RF) components shown in FIG. 11.

[0191]FIG. 20 is a top view of a thin-walled metal shell 621 which actsas a base for the control module 620. FIG. 21 is a cross section of thecontrol module 620 and also shows the cross section of the shell 621 asindicated by the section 21-21 in FIG. 20. FIGS. 20 and 21 show that theshell 621 has a flange 622 and four holes through which are insertedbone screws 623 that attach the shell 621 to the bony structure of thecranium. Also shown in FIG. 20 and 21 are input wires (of which onlywire 611 is indicated) that enter the insulating strain relief structure640. On the interior of the shell 621 are male connecting pins 641 whichare designed to mate with a female receptacle which forms part of theelectronics module 626 that is shown in FIG. 21. The electronics module626 contains most if not all of the electronic circuitry that iscontained within the control module 620. Also shown in FIG. 21 is thebattery 625 which has a top plate 624 that extends over the flange 622of the shell 621. An 0-ring 627 is used to provide a fluid seal toprevent body fluids from entering the control module 620. A siliconerubber adhesive or small metal screws could be used to join the topplate 624 to the flange 622 of the shell 621. The shell 621, battery625, and electronics module 626 constitute the three major parts of thecontrol module 620.

[0192] The control module 620, is designed for easy implantation withina space in the cranium where the bone has been removed. The thickness ofthe cranium at the site of the implantation would be approximately 10mm. Therefore, the thickness of the control module 620 would beapproximately the same 10 mm with a diameter of approximately 40 mm. Toimplant the control module 620, the hair would be shaved over theimplantation site, an incision would be made in the scalp, and the bonewould be removed to make room for the control module 620. In a similarmanner, holes such as H1-H4 inclusive would be made in the cranium forthe pass-through of wires connecting to the brain electrodes.

[0193] Although FIG. 21 shows the electronics module 626 located beneaththe battery 625, it also envisioned that those positions could bereversed if such positioning offered a more advantageous construction.In either case, either the battery 625 or the electronics module 626could be readily replaced through a simple incision in the scalp overthe site of the implanted control module 620 after the hair has beenremoved from the incision site.

[0194]FIG. 22 illustrates an alternative embodiment of the invention inwhich the system 700 for the treatment of neurological disordersutilizes a control module 720 that is located in the patient's chest.The system 700 uses epidural electrodes 701, 702 and 703 and a deepelectrode 701D; the electrodes being joined by connecting wires 711,712, 713 and 711D, respectively, through a wire cable 710 to the controlmodule 720. The electrode 701 is shown placed at an epileptic focus 730.This system can be used in exactly the same manner as previouslydescribed for the system 10 that had a control module 20 that was placedwithin the cranium.

[0195]FIG. 23 illustrates another embodiment of the invention whichutilizes a control module placed between the patient's scalp and craniumand a remotely located implantable sensor/actuator device 850 locatedwithin the patient's body but not in the patient's head. The system 800could operate in one of two modes. In the first mode, thesensor/actuator device 850 would operate as a sensor for sensing somephysiological condition such as an elevated blood pressure or anelectrical signal from a nerve or muscle indicating the presence ofpain. The active electrode 854 is connected by the wire 851 to thesensor/actuator device 850 using the metal case of the sensor/actuatordevice 850 as an indifferent electrode. An electrical signal in thefrequency range 1 to 500 kHz emitted from the electrode 854 could beused to communicate with the control module 820, thus providing asignaling means to the control module 820 from the remotesensor/actuator device 850. Of course, such signaling means can also beprovided from the control module 820 to the sensor/actuator device 850.The electrical signal from the sensor/actuator device 850 would bedetected between the active electrode 801 and an indifferent electrodethat could be the metal case of control module 820 or it could be aseparate electrode. The active electrode 801 is connected to the controlmodule 820 by the connecting wire 811. It should be noted that in FIG.23, the electrode 801 is placed epidurally at the bottom of the hole H8.This can be a comparatively simple way to place an epidural electrode.

[0196] Having received a signal from the sensor/actuator device 850acting as a sensor, the control module 820 would send a signal via thewire 812 to electrode 802 to act on that portion of the brain that wouldresult in a treatment of the physiological condition that caused thesensor/actuator device 850 to communicate with the control module 820.Thus, for example, if the electrode 854 detects a pain signal from anerve in the back, the electrode 802 could be used to turn off a certainregion of the brain so that the patient would not perceive that pain.

[0197] A second mode of operation for the system 800 would be when theintracranial portion of the system 800 is used for sensing an adversephysiological condition, and the sensor/actuator device 850 is used asan actuator to carry out some treatment at a remote location toameliorate that adverse physiological condition. In this mode, theelectrode 802 would sense the adverse condition and send an alternatingelectrical signal out from electrode 801 to carry out some treatment ata remote location within the body. The electrode 854 would receive thatsignal and could cause the sensor/actuator device 850 to carry out apre-programmed treatment. For example, if a migraine headache isperceived by the control module 820, the sensor/actuator device 850could be instructed to release medication via the catheter 853 into thecerebrospinal fluid (the CSF) to relieve that headache. Or a Parkinson'sdisease tremor might be detected and the neurotransmitter epinephrinewould be appropriately released into the CSF to relieve that tremor. Inanother example, if the patient thought about moving a certain musclethat had been made inoperative due to interrupted nerve conduction, thatmuscle could be activated by the electrode 856 which is connected by thewire 852 to the sensor/actuator device 850.

[0198] It should be understood that the communication signal meansbetween the control module 820 and the sensor/actuator device 850 couldbe modulated by any one of several well known techniques (such as AM,FM, phase modulation, etc.) in order to carry out proportional responsesbased upon the sensing signal received by the electrode 802 andprocessed by the control module 820. It should also be understood thatcommunication between the control module 820 and the remotesensor/actuator device 850 could be accomplished by acoustic (e.g.ultrasonic) vibrations from a buzzer at either location to a microphoneat the receiving end of the transmission or by any suitableelectromagnetic communication means. Of course it is also understoodthat a multiplicity of electrodes could be used with either the controlmodule 820 or the sensor/actuator device 850, and that both the controlmodule 820 and the remote sensor/actuator device 850 might togetherproduce the response to a detected event.

[0199] It is further envisioned the signaling means between the controlmodule 820 and the remote sensor/actuator device 850 may be in the formof either analog or digital signals.

[0200]FIG. 23 also illustrates how a buzzer 95 connected by the wires 92to a control module 820 could be used as part of the means for stoppinga neurological event such as an epileptic seizure. Since the buzzercould be located in close proximity to the ear, if it produces anacoustic output when an epileptic seizure is detected by the controlmodule 820, that acoustic input into the brain can stop the epilepticseizure. Furthermore, a hearing aid type of acoustic output device 895placed in the ear could have an acoustic output of a particularintensity and pitch that could turn off the seizure. The operation ofeither the buzzer 95 or the acoustic output device 895 would beautomatic, i.e., when a seizure precursor is detected, an acoustic inputsignal would be applied automatically. The device 895 could be actuatedby receiving a signal from the buzzer 95.

[0201]FIG. 23 also shows a visual light source 896 that could be a lightemitting diode in eyeglasses worn by the patient or a special flashlighttype of device. Either device could be used with a particular wavelengthof light and rate of flashing on and off so as to provide a visual inputthat could act as a means for stopping an epileptic seizure. Althoughthe light source 896 could be automatic if it were on a pair ofeyeglasses, if a flashlight type of device is used, the visual inputwould be manually applied.

[0202] Also shown in FIG. 23 is a sensory actuator 897 which can applyelectrical stimulation to electrodes 898 through wires 899 to thepatient's skin. The sensory actuator 897 might also produce mechanicalvibrations applied directly to the patient's skin.

[0203]FIG. 24 shows an alternative embodiment of the invention, whichuses a multiple pin, pyrolytic carbon receptacle 911 placed through thepatient's scalp which provides a multiplicity of electrical connectionsfor the control module 920. Specifically, the system 900 has a controlmodule 920 that is electrically connected to the receptacle 911 by meansof the wire cable 922. The mating plug 912 is connected by the cable 913to provide two-way communication via electrical wires between thecontrol module 920 and the external equipment 11. The plug 912 and cable913 can also be used with the charging equipment 914 to recharge arechargeable battery (not shown) located in the control module 920.

[0204] Also shown in FIG. 24 are other alternative means for providingtwo-way communication between the control module 920 and the externalequipment 11. Specifically, FIG. 24 shows an acoustic (ultrasonic)transducer 931 mounted on the control module 920 that can communicatewith the externally located transducer 932 which is in two-waycommunication with the external equipment 11 through the wire cable 933.In a similar manner, an infrared emitter/receiver 941 can send aninfrared signal through the patient's scalp to an infraredemitter/receiver 943 that is connected by the wire cable 943 to theexternal equipment 11.

[0205] By any of these methods, either direct electrical connection, oracoustic or infrared two-way communication the equivalent function ofelement 72 in FIG. 2 can be accomplished. It has already beenestablished that two-way communication 72 can also be accomplished by avariety of electromagnetic means including an alternating magnetic fieldor by radio frequency communication.

[0206]FIG. 24 also shows other locations for electrodes that are to beplaced in close proximity to the brain. Specifically, FIG. 24 shows anelectrode 950 mounted on the outer surface of the scalp that isconnected by the cable wire 951 to the control module 920. Such anexternal electrode 950 could also be used with an externally placedcontrol module (not shown). Additionally, electrodes such as theelectrode 960 could be placed between the patient's scalp and craniumand would be connected by the wire cable 961 to the control module 920.Furthermore, electrodes such as the electrode 950 could be placedbetween the dura mater and the arachnoid and would be connected via thewire cable 971 to the control module 920.

[0207] It should be noted that any of the electrodes described hereinthat are in the general proximity of the brain either inside or on topof the patient's head or deep within the patient's brain can all beconsidered to be “brain electrodes.”

[0208]FIG. 25 illustrates a system 980 for the treatment of neurologicaldisorders that uses an external control module 990 with either internalor external means for stopping a neurological event. Specifically, thescalp mounted electrode 994 connected by the wire 996 to the controlmodule 990 could be used to detect a neurological event. Of course onecould use a multiplicity of such scalp-mounted electrodes. Once aneurological event has been detected, the control module 990 couldactuate an acoustic input device 895, or a visual light input device 986or an actuator 897 for other sensory inputs. Thus, such a system 980envisions a control module 990 mounted external to the patient that usesexternal remote actuators that can provide acoustic, visual or othersensory inputs that could stop an epileptic seizure.

[0209] Furthermore, the system 980 envisions the use of the externallymounted control module 990 with electrodes mounted in close proximity tothe brain or actually within the brain (i.e. “brain electrodes”).Specifically, the electrodes 801 and 802 could be mounted on the duramater and a deep electrode 801D could be placed within the brain itself.The wires 811, 812 and 811D could be connected to receptacle 982 that ismated to the plug 984 that connects by the wire 992 to the controlmodule 990. The electrodes 801, 802 and 801D could be used either forsensing a neurological event or for providing an electrical stimulationto stop such a neurological event.

[0210] In FIG. 25, the remote sensor/actuator device 850 can be used aspart of the means for stopping a neurological event by applying anelectrical stimulus to one or two vagus nerves by means of theelectrodes 854 and/or 856. This could also be accomplished using thesystem shown in FIG. 23, i.e., with any control module 820 (or 20) thatis implanted beneath the scalp. In FIG. 25 the catheter 853 can be usedto apply medication as part of the means for stopping a neurologicalevent. The sensor/actuator device 850 can be triggered to stop theneurological event by means of a signal originating from the externallymounted control module 990.

[0211] Also shown in FIG. 25 is an external remote actuator 897 whichcan apply electrical stimulation to electrodes 898 through wires 899 tothe patient's skin. The actuator 897 might also produce mechanicalvibrations applied directly to the patient's skin as another form ofsensory input.

[0212] Additional objects and advantages of the present invention willbecome apparent to those skilled in the art to which this inventionrelates from the subsequent description of the preferred embodiments andthe appended claims, taken in conjunction with the accompanyingdrawings.

What is claimed is:
 1. A method for providing responsive therapy to apatient with epilepsy, comprising the steps of: receiving an EEG signalwith an implanted control module; detecting a neurological event in theEEG signal; and performing an action in response to the detectedneurological event; wherein the action provides a therapeutic effect tothe patient.
 2. The method for providing responsive therapy of claim 1 ,further comprising the step of processing the EEG signal with anelectronic circuit in the implanted control module.
 3. The method forproviding responsive therapy of claim 2 , wherein the electronic circuitcomprises an event detection subsystem.
 4. The method for providingresponsive therapy of claim 1 , further comprising the step ofconverting the EEG signal into a digital data stream.
 5. The method forproviding responsive therapy of claim 4 , wherein the digital datastream is representative of the EEG signal.
 6. The method for providingresponsive therapy of claim 4 , wherein the digital data stream isrepresentative of an energy spectrum of the EEG signal.
 7. The methodfor providing responsive therapy of claim 4 , further comprising thestep of processing the digital data stream.
 8. The method for providingresponsive therapy of claim 7 , wherein the step of processing thedigital data stream employs a digital signal processor.
 9. The methodfor providing responsive therapy of claim 4 , wherein the step ofdetecting a neurological event comprises performing a detectionalgorithm on the digital data stream.
 10. The method for providingresponsive therapy of claim 9 , wherein the step of performing thedetection algorithm comprises the steps of: extracting a characteristicfrom the digital data stream; comparing the characteristic of thedigital data stream to a threshold; and if the characteristic exceedsthe threshold, indicating that a neurological event has been detected.11. The method for providing responsive therapy of claim 10 , whereinthe characteristic comprises an energy of the EEG signal in a frequencyband.
 12. The method for providing responsive therapy of claim 10 ,wherein the characteristic comprises a signal amplitude.
 13. The methodfor providing responsive therapy of claim 10 , wherein thecharacteristic comprises a signal event density within a time period.14. The method for providing responsive therapy of claim 1 , wherein thestep of performing an action comprises delivering an electricalstimulation signal to a brain of the patient.
 15. The method forproviding responsive therapy of claim 14 , wherein the step ofdelivering an electrical stimulation signal comprises the steps of:generating the electrical stimulation signal; and transmitting theelectrical stimulation signal to a stimulation electrode via a lead. 16.The method for providing responsive therapy of claim 15 , wherein thestimulation electrode is implanted in the brain of the patient.
 17. Themethod for providing responsive therapy of claim 14 , wherein theelectrical stimulation signal includes a pulse.
 18. The method forproviding responsive therapy of claim 17 , wherein the pulse isbiphasic.
 19. The method for providing responsive therapy of claim 1 ,wherein the step of performing an action comprises actuating a buzzer tocause an acoustic signal to be perceived by the patient.